U.S. patent number 4,626,244 [Application Number 06/697,514] was granted by the patent office on 1986-12-02 for implantable medication infusion device.
This patent grant is currently assigned to Consolidated Controls Corporation. Invention is credited to Robert H. Reinicke.
United States Patent |
4,626,244 |
Reinicke |
December 2, 1986 |
Implantable medication infusion device
Abstract
An integral fluid filter and capillary restrictor unit, or
alternatively an integral fluid filter and multiple orifice
restrictor unit, is resiliently positioned in a manifold body which
is edge mounted to a flat cylindrical assembly which contains the
medication reservoir and pressure stabilizing chamber to provide a
completely self contained implantable unit which is thin, small and
light weight and yet needs to be refilled only as often as the much
larger stainless steel capillary tube devices with bellows type
reservoirs now on the market.
Inventors: |
Reinicke; Robert H. (Mission
Viejo, CA) |
Assignee: |
Consolidated Controls
Corporation (El Segundo, CA)
|
Family
ID: |
24801423 |
Appl.
No.: |
06/697,514 |
Filed: |
February 1, 1985 |
Current U.S.
Class: |
604/141;
128/DIG.12; 604/151; 604/892.1 |
Current CPC
Class: |
A61M
5/141 (20130101); A61M 5/14276 (20130101); A61M
5/16877 (20130101); A61M 5/14586 (20130101); Y10S
128/12 (20130101); A61M 2205/0244 (20130101); A61M
5/16804 (20130101) |
Current International
Class: |
A61M
5/142 (20060101); A61M 5/145 (20060101); A61M
5/168 (20060101); A61M 005/00 () |
Field of
Search: |
;604/51-53,131,132,141,151,890-892,896 ;128/DIG.12 |
References Cited
[Referenced By]
U.S. Patent Documents
Primary Examiner: Pellegrino; Stephen C.
Attorney, Agent or Firm: Mason, Kolehmainen, Rathburn &
Wyss
Claims
What is claimed as new and desired to be secured by Letters Patent
of the United States is:
1. An implantable medication infusion device, comprising a pair of
circular concave members positioned in opposed relation with the
outer edges thereof connected together, a flexible circular
diaphragm positioned between said concave members and having the
edge thereof sealed to said concave members thereby to form a
pressure stabilizing chamber with one of said concave members on
one side of said diaphragm and a medication reservoir with the
other one of said concave members on the other side of said
diaphragm, a two phase fluid in said pressure stabilizing chamber
for maintaining a constant pressure on said diaphragm which is
greater than the body pressure of the body in which said infusion
device is implanted, body means secured to at least one of said
concave members and having a recess therein, a penetrable septum
mounted in said body means and communicating with said recess a
passageway in said body means between said recess and said
reservoir, whereby said reservoir can be filled through said
septum, said recess and said passageway, and a capillary unit
positioned in said body means and having an inlet connected to said
reservoir and an outlet communicating with the exterior of said
device, said capillary unit having a flow restrictive passageway
between said inlet and outlet of sufficiently small cross section
to limit the flow of medication from said reservoir in response to
the pressure on said diaphragm to a desired rate.
2. The medication infusion device of claim 1, wherein said
capillary unit comprises a silicon substrate having a capillary
groove formed in one surface thereof and connected between said
inlet and said outlet, and a glass plate bonded to said surface of
said silicon substrate to form with said substrate said flow
restrictive passageway.
3. The device of claim 2, which includes means for establishing a
seal between said inlet and said outlet of said capillary unit
positioned in said body means.
4. The device of claim 3, wherein said capillary unit is positioned
in an opening in one side of said body means and a cover is seated
in said opening, said sealing means comprising first O-ring means
between said capillary unit and said cover and second O-ring means
between said capillary unit and said opening in said body
means.
5. The device of claim 4, wherein said body means includes a second
passageway extending from the bottom of said recess inside said
second O-ring means to the exterior of said body.
6. The device of claim 2, wherein said inlet of said capillary unit
comprises a first opening in said plate and communicating with one
end of said groove, and said outlet comprises a second opening in
said glass plate and communicating with the other end of said
groove.
7. The device of claim 2, wherein said capillary unit also includes
inlet filter means connected between said inlet and one end of said
capillary groove, and outlet filter means connected between the
other end of said capillary groove and said outlet.
8. The device of claim 7, wherein said inlet filter means comprises
a first series of parallel grooves in said silicon substrate and
said outlet filter means comprises a second series of parallel
grooves in said silicon substrate, the cross sectional area of the
grooves in said second series being substantially greater than the
cross sectional area of the grooves in said first series.
9. The device of claim 8, wherein said inlet includes an opening in
said glass plate and said first series of parallel grooves are
positioned in groups around said opening.
10. The device of claim 8, wherein said outlet includes an opening
in said glass plate and said second series of parallel grooves are
positioned in groups around said opening.
11. The device of claim 10, wherein said group of second parallel
grooves are arranged along the four sides of a rectangle within
which is positioned said opening.
12. The device of claim 11, which includes a collector groove
formed in said surface and interconnecting the outer ends of all of
said groups of second parallel grooves, said collector groove also
being connected in said other end of said capillary groove.
13. The device of claim 8, wherein said inlet includes an opening
in said silicon substrate and said first series of parallel grooves
are positioned in groups around said opening.
14. The device of claim 8, wherein said outlet includes an opening
in said silicon substrate and said second series of parallel
grooves are positioned in groups around said opening.
15. The device of claim 2, wherein said inlet of said capillary
unit comprises a first opening in said silicon substrate and
communicating with one end of said groove, and said outlet
comprises a second opening in said silicon substrate and
communicating with the other end of said groove.
16. The device of claim 1, wherein said device has a maximum
thickness of one half inch.
17. An implantable medication infusion device, comprising a pair of
circular concave members positioned in opposed relation with the
edges thereof connected together to form a housing, a flexible
diaphragm mounted within said housing to provide a pressure
stabilizing chamber with one of said concave members and a
medication reservoir with the other of said concave members, a
two-phase fluid in said pressure stabilizing chamber for
maintaining a constant pressure on said diaphragm which is greater
than the body pressure of the body in which said infusion device is
implanted, a manifold body offset from the edge of said housing and
having a neck portion connected to one of said concave members,
said manifold body having a chamber therein which is connected to
said reservoir through a passageway in said neck portion, a
penetrable septum mounted in said body and communicating with said
chamber, whereby said reservoir can be filled by supplying
medication through said septum said chamber and said passageway,
and a capillary unit positioned in said chamber and having an inlet
connected to said chamber and an outlet communicating with the
exterior of said device, said capillary unit having a flow
restrictive conduit between said inlet and said outlet of
sufficient length and having a sufficiently small cross section to
limit to a desired rate the flow of medication from said reservoir
and through said passageway in response to the pressure exerted on
said diaphragm by said two-phase fluid.
18. The device of claim 17, wherein the thickness of said offset
manifold body is approximately equal to the thickness of said
housing.
19. An implantable medication infusion device, comprising a
medication reservoir having a movable wall portion, a pressure
stabilizing chamber in communication with said movable wall
portion, a two phase fluid in said pressure stabilizing chamber for
maintaining a constant pressure on said movable wall portion which
is greater than the body pressure of the body in which said
infusion device is implanted, a catheter outlet communicating with
the exterior of said device, and a flow restrictor unit interposed
between said reservoir and said catheter outlet, said flow
restrictor unit comprising a large number of serially connected
orifices which collectively limit the flow of medication from said
reservoir in response to the pressure on said movable wall portion
to a desired rate.
20. The medication infusion device of claim 19, wherein said flow
restrictor unit comprises a silicon substrate having a large number
of minute grooves formed in one surface thereof and serially
interconnected along a predetermined flow path, and a glass plate
bonded to said surface of said silicon substrate to form with said
minute grooves a series of orifice type restrictions which
collectively limit the flow of medication from said reservoir to
said desired rate.
21. The medication infusion device of claim 20, wherein said minute
grooves are interconnected by means of troughs formed in said
surface of said silicon substrate which are of much greater depth
than said minute grooves.
22. The medication infusion device of claim 21, wherein said
troughs comprise V-shaped grooves formed in the surface of said
substrate and extending transversely of said flow path.
23. The medication infusion device of claim 22, wherein said
troughs have a length transverse to said flow path of approximately
ninety microns.
24. The medication infusion device of claim 22, wherein said
troughs have a width along said flow path of approximately
sixty-nine microns.
25. The medication infusion device of claim 22, wherein said
troughs have a depth of approximately twenty-eight microns.
26. The medication device of claim 22, wherein said troughs are
spaced apart by approximately two microns along the surface of said
substrate.
27. The medication infusion device of claim 20, wherein said minute
grooves each have a width of approximately 8 microns.
28. The medication infusion device of claim 20, wherein said minute
grooves each have a depth of 5.7 microns.
29. The medication infusion device of claim 20, which includes
inlet filter means formed in said surface of said substrate and
connected to one of said minute grooves at one end of said flow
path.
30. The medication infusion device of claim 29, which includes
outlet filter means formed in said surface of said substrate and
connected to one of said minute grooves at the other end of said
flow path.
31. The medication infusion device of claim 30, wherein said outlet
filter means comprises a second series of parallel grooves formed
in said surface of said silicon substrate and each having a width
of approximately six microns.
32. The medication infusion device of claim 29, wherein said inlet
filter means comprises a first series of parallel grooves formed in
said surface of said silicon substrate and each having a width of
approximately four microns.
Description
BACKGROUND OF THE INVENTION
The present invention relates to implantable medication infusion
devices, and, more particularly to such devices which are arranged
to provide a continuous unprogrammed flow of medication into the
body.
Medication infusion devices of the continuous flow type shown in
Blackshear et al U.S. Pat. No. 3,731,681 and in the article by B.
M. Wright entitled "A Portable Slow Infusion Capsule" in the
Journal of Physiology March 1965, Vol. 177 No. 1 (Cambridge
University Press) and devices similar to the Blackshear patent are
presently available on the market. In such devices a relatively
constant pressure is exerted on a flexible diaphragm or bellows
which contains a reservoir of medication. The pressure exerted on
the bellows is above body pressure so that medication is forced out
of a long capillary tube, which is used as a flow limiting
resistance device, and delivered to the infusion site within the
body. This capillary tube is usually made of stainless steel and a
length of 50 feet may be required to provide sufficient resistance
to flow for desired delivery rates of medication even when the tube
is fabricated to the minimum practical inside diameter of 0.004
inches. This stainless steel capillary tube is wrapped around the
outside of the implantable device, or in a recess in the outside of
the housing of such device as shown in Blackshear U.S. Pat. No.
3,731,681, and the end of the capillary tube is connected to a
flexible catheter which is positioned at the infusion site in the
body.
When such a long stainless steel capillary tube is used the
medication remains in contact with the stainless steel for many
hours, or even days, at relatively low infusion rates and this long
residence or dwell time within the capillary tube causes problems
of compatibility with the medication, particularly when a
medication such as insulin is used. When a stainless steel
capillary tube is used the medication is also more likely to
precipitate out and clog the capillary tube. While titanium is more
compatible to the medication and is less likely to clog, it is
impossible to fabricate a titanium capillary tube of such small
diameter. When it is desired to provide different flow rates with
such a stainless steel capillary tube, each device must be tested
separately after it is manufactured and the length of the capillary
tube is trimmed down and then retested to get a particular infusion
rate.
It is often necessary to mix the medication with a high viscosity
diluent for use in existing continuous infusion devices in order to
limit the capillary tube to a practical length, such as 50 feet.
Using a high viscosity diluent makes the medication less potent
while increasing the viscosity of the medication solution, and
since capillary tube length is directly proportional to medication
solution potency and inversely proportional to its viscosity, both
of these effects reduce the length of capillary tube. For example,
it is not feasible to deliver standard, undiluted 100 unit insulin
to diabetic patients with existing devices. By diluting 100 unit
insulin with 80% glycerol it is possible to use these devices but
they must have large (typically 30 to 50 milliliters) reservoirs to
contain the diluted medication and such a large reservoir requires
the use of a flexible multiple convolution bellows rather than a
single diaphgram, thus making the devices large and heavy and not
suitable for implantation in children and less than average size
adults. Such bellows type devices suffer from the additional
disadvantage that they have many crevices ano a much higher
residual and unusable medication volume than the diaphragm type of
reservoir.
The infusion rate of existing continuous infusion devices also
varies considerably due to changes to patient body pressure and
changes in patient body temperature. Body pressure change, which
varies the pressure at the outlet of the catheter and capillary
tube restrictor, is due to variations in altitude which changes the
ambient atmospheric and body pressure of the patient. Also, normal
small changes (as well as abnormal changes due to sickness) in
patient body temperature change the vapor pressure of the
medication reservoir pressurant, thus changing the pressure at the
inlet of the capillary tube restrictor. Therefore, both altitude
and temperature changes act to vary the pressure drop across the
capillary tube restrictor and the infusion rate through the
capillary tube, which is directly proportional to this pressure
drop. For example, if the patient travels from sea level to 10,000
feet above sea level, the drug infusion rate of existing devices
increases by a factor of 2.5. If the patient temperature should
also happen to increase from 97.degree. F. to 101.degree. F., the
combined effect of the altitude and temperature changes would
increase the infusion rate by a factor of 3.5. This large infusion
rate variation can severely limit the clinical effectiveness and
benefits for many continuous drug infusion treatments.
In Barth application Ser. No. 616,658 filed June 4, 1984 an
integral fluid filter and capillary arrangement is disclosed in
which the capillary is formed by a groove etched in the surface of
silicon substrate by conventional semiconductor processing
techniques and a glass plate is bonded to said surface of the
substrate to form a long capillary groove of very small cross
sectional area. A plurality of parallel grooves of smaller cross
sectional area are also etched in the substrate surface to provide
a comb filter at each end of the capillary groove.
SUMMARY OF THE INVENTION
The arrangement of the present invention avoids all of the above
discussed difficulties experienced with a stainless steel capillary
tube by employing an integral fluid filter and capillary groove
restrictor arrangement generally similar to that described in said
Barth application, or, in the alternative, an integral filter and
multiple orifice restrictor arrangement. The integral fluid filter
and restrictor unit is resiliently positioned in a manifold body
which is edge mounted to a flat cylindrical assembly which contains
the medication reservoir and pressure stabilizing chamber to
provide a completely self contained implantable unit which is thin,
small and light weight and yet needs to be refilled only as often
as the much larger stainless steel capillary tube devices with
bellows type reservoirs now on the market. The silicon and glass
surfaces of the integral filter and restrictor unit are highly
compatible with medication such as insulin. Also, due to the
extremely small, precise cross sectional area of the restrictor
groove in the silicon substrate a much greater restriction per unit
length is provided so that the overall restriction is much greater
while greatly reducing the overall length of the restrictor groove
with a corresponding reduction of the dwell time of the medication
within the restrictor groove. As a result, full strength
medication, such as insulin, may be utilized in the reservoir of
the implantable device so that the reservoir is much smaller, thus
making the device much smaller and lighter than devices now
available which have large reservoirs to contain diluted (as much
as 80%) medication. Furthermore, the use of maximum strength
medication, such as insulin, facilitates the provision of a lower
medication delivery rate so that a smaller volume reservoir in the
device of the present invention lasts as long as the much larger
devices now being used before refill is needed. For example, with a
restrictor groove of only 6.4 inches total length sufficient flow
restriction is provided to give a continuous flow rate of 10
microliters per hour of 100 unit insulin and the insulin is within
the flow restrictor groove for only about 80 seconds. The 10
microliters per hour of 100 unit insulin used in this example
delivers 1 unit per hour of insulin, which is the nominal basal
infusion rate required for Type I diabetics.
Since the silicon and glass integral filter and restrictor groove
unit can be manufactured with minimum feature sizes of only a few
microns (micrometers), it is very easy to fabricate miniature
restrictor units that are much more restrictive than needed for the
delivery of standard, full strength medications that are now
commercially available. Therefore, with the arrangement of the
present invention, pharmaceutical drug suppliers will have a market
for more potent medications so that the implantable devices can be
made even smaller and lighter, and then could be used by children
and even infants.
With such an integral filter and restrictor unit it is also
possible to use a different two phase pressurant having a greater
vapor pressure (which requires a more restrictive integral filter
and restrictor unit) in the stabilizing chamber of the drug
reservoir to reduce the undesirable variation of infusion rate due
to altitude and temperature changes. For example, the
aforementioned 2.5 factor increase of infusion rate when the
patient travels from sea level to 10,000 feet altitude is reduced
to a factor of 1.5 by using Freon 11, also called Freon MF, (vapor
pressure equal to 23 psia at 98.6.degree. F.) produced by E. I.
DuPont Company, in place of the FC-87 or FC-88 Perfluorocarbon
(vapor pressure equal to 17.5 psia at 98.6.degree. F.), produced by
the 3M Company, now being used. Although there is a slight weight
increase because of the stiffer structure needed to contain the
higher pressure, this device is still much lighter than existing
devices.
In accordance with a further aspect of the invention, the infusion
rate variation can also be reduced by replacing the capillary type
groove with a series of miniature orifices, since flow rate through
an orifice is proportional to the square root of its pressure drop,
not directly proportional as in a capillary. But because the
infusion rate is extremely small, its velocity pressure is quite
low, the orifices must be very small and many orifices are needed
in series to create sufficient pressure drop. For example, using
anisotropic etched orifices each having a maximum feature dimension
of only 8 microns, 2530 series orifices are needed to limit the
infusion rate to 10 microliters per hour using FC-87 or FC-88
Perfluorocarbon pressurant at normal body temperature, 98.6.degree.
F. It is not possiole to use conventional metal machining or metal
chemical milling processes to fabricate this very small size and
large number of orifices in a metal such as titanium. However,
miniature precision orifices can be easily fabricated in silicon
using standard lithography and masking processes that are used to
manufacture solid state electronic chips and micromachining
techniques such as described in an article entitled "Silicon
Micromechanical Devices" by James B. Angell, Stephen C. Terry and
Phillip W. Barth which appeared in the April, 1983 issue of
Scientific American, pp. 44-55. Using this flow restriction
technique, the aforementioned 2.5 factor increase of infusion rate
when the patient travels from sea level to 10,000 feet altitude is
reduced to a factor of 1.6. This accomplishes a significant
improvement of infusion rate regulation without any weight
increase, but the integral filter and multiple orifice restrictor
may be somewhat more expensive than the capillary groove type
because the filter and orifice features are smaller and processing
controls need to be more exact to hold closer dimensional
tolerances.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention, both as to its organization and method of operation,
together with further objects and advantages thereof, will best be
understood by reference to the following specification taken in
connection with the accompanying drawings, in which:
FIG. 1 is a plan view of the implantable medication infusion device
of the present invention;
FIG. 2 is a sectional view taken along the lines 2--2 of FIG.
1;
FIG. 3 is a sectional view taken along the lines 3--3 of FIG.
1;
FIG. 4 is a sectional view taken along the lines 4--4 of FIG. 1 but
with the catheter assembly omitted;
FIG. 5 is a greatly expanded plan view of the integral fluid filter
and capillary unit employed in the device of FIG. 1;
FIG. 6 is a sectional view taken along the lines 6--6 of FIG.
5;
FIG. 7 is a fragmentary sectional view similar to FIG. 2 but on an
expanded scale and showing the body stem-reservoir seal of the
implantable device;
FIG. 8 is a fragmentary sectional view similar to FIG. 2 but on an
expanded scale and showing the pressure stabilizing chamber seal of
the implantable device;
FIG. 9 is a sectional view similar to FIG. 6 but on an enlarged
scale of the different groove configurations in the integral filter
and capillary unit of the implantable device of FIG. 1;
FIG. 10 is a fragmentary plan view of an alternative embodiment
employing a multiple orifice flow restrictor;
FIG. 11 is a sectional view taken along line 11--11 of FIG. 10,
and
FIG. 12 is a sectional view taken along line 12--12 of FIG. 10.
Referring now to the drawings, and more particularly to FIGS. 1-9
thereof, the implantable medication infusion device of the present
invention is therein illustrated as comprising a flat circular
housing, indicated generally at 10, which is formed oy the opposed
dish-shaped circular members 12 and 14. A flexible corrugated
diaphragm 16 is positioned between the members 12 and 14 to define
a medication reservoir 18 and a pressure stabilizing chamber 20
with the members 12 and 14, respectively. A manifold body indicated
generally at 22 is offset from the edge of the housing 10 and is
connected to the housing member 12 through a neck portion indicated
generally at 24, the body 22 being positioned in line with the
housing 10 so that the overall thickness of the implantable device
of the present invention is minimized. More particularly, the neck
portion 24 includes a fan shaped portion 26 (FIG. 1) which is
secured to the member 12 at the edge 28 thereof by welding or
brazing, and a central raised portion 30 within which the
passageway 32 is provided. The passageway 32 interconnects a recess
34 in the manifold body 22 and the reservoir 18 through a body stem
element 36 having the central opening 38 therein.
An integral medication filter and capillary unit indicated
generally at 40 is resiliently mounted within the recess 34, the
unit 40 being preferaoly constructed and arranged as described in
detail hereinafter in connection with FIGS. 5 and 6. Specifically,
a first O-ring 42 is positioned in the groove 44 formed in the
bottom of the recess 34 and an O-ring 46 is positioned immediately
above the O-ring 42 in a groove 48 formed in the recess cover
member 50 which is sealed to the housing 22 by means of the weld 52
after the unit 40 has been installed.
In order to permit refilling of the reservoir 18, a penetrable
septum 60 is mounted in the body 22 so that a hypodermic needle may
be inserted through the septum 60 into the chamber 62 formed in a
needle stop member 64, the needle being inserted until it strikes
the wall 66 of the needle stop 64. The needle stop 64 is sealed to
the body 22 by means of the weld 68 after the penetrable septum 60
has been positioned in the stepped recess 70 formed in the body 22.
The septum 60 may be made of medical grade silicone elastomer or
medical grade bromobutyl elastomer. Bromobutyl elastomer is
preferred because of its lower permeation rate, both for permeation
of the medication out of the septum 60 and also for permeation into
the septum of the dissolved gases in the body fluids which surround
the implanted device.
The needle stop 64 is provided with a passage 72 which communicates
with the recess 34 in the body 22 through the passageway 74
therein. The body 22 is provided with a slightly raised conical
section 76 which is provided with the flared central recess 78
communicating with the septum 60, the flared walls 80 of the recess
78 acting to guide the needle to the surface 82 of the septum 60 as
the needle is inserted. The slightly raised portion 76 with its
central recess 78 facilitates the location of the implanted device
by the doctor during a refilling operation. Once a needle has been
inserted into the chamber 62, medication can be supplied from this
chamber through the passageway 72, 74, the recess 34, the
passageway 32 in the neck portion 30 and the central opening of the
body stem 36 into the medication reservoir 18. A standard
disposable syringe and hypodermic needle can be used to refill the
implanted device. It will be noted that during this filling
procedure the integral filter and capillary unit 40 is effectively
bypassed since the chamber 34 communicates directly with the
passageway 32 leading to the reservoir 18.
The pressure stabilizing chamber 20 is filled with a fluid which
through a change of state establishes a substantially constant
pressure on the medication within the reservoir 18 despite changes
in the volume of medication within this reservoir and changes in
temperature and pressure within the body. The pressure stabilizing
chamber 20 may be filled in accordance with the procedure described
in detail in my copending application Ser. No. 554,197, filed Nov.
22, 1983, and reference may be had to said application for a
detailed description of such filling procedure. However, since the
implantable device of the present invention is arranged to provide
a continuous unprogrammed flow of medication into the body in
response to this constant pressure, the two phase fluid must
establish a stabilized pressure which is substantially above body
pressure in order to force the medication through the filter and
capillary unit 40 and into the body. Accordingly, the chamber 20 is
preferrably filled with a perfluorocarbon compound which is
preferably of the type No. FC-87 or FC-88 manufactured by Minnesota
Mining and Manufacturing Company, Inc. At body temperature this
fluid creates a pressure of about 17.5 psia so that at an
atmospheric pressure of 14.7 psia approximately 2.8 psi is
available to drive the medication through the unit 40 and into the
body.
During the filling procedure the outer edge of the diaphragm 16 is
sealed to the outer lip portion 84 of the housing member 14 before
the members 12 and 14 are joined together. This subassembly is then
clamped to a fixture which simulates the curved surface of the
member 12 so that a simulated reservoir 18 is provided between the
diaphragm 16 and this fixture. A small central opening 86 FIG. 8 is
provided in the member 14 through which the perfluorocarbon fluid
is admitted.
Considering now the manner in which the chamber 20 is filled and
sealed, the perfluorocarbon fluid is first vacuum conditioned to
remove most of the absorbed air. This fluid and the simulated
reservoir-pressure chamber subassembly are then heated to
90.degree. F. After a vacuum is pulled in the chamber 20 and in the
simulated reservoir 18 in the fixture, the heated perfluorocarbon
fluid is introduced into both of these chambers so that initially
there is no pressure differential across the diaphragm 16. A 10 to
20 psig nitrogen (or air) gas pressure is then applied through the
fixture to the medication side of the diaphragm 16 which expels
most of the perfluorocarbon fluid within the chamber 20 out of the
hole 86 and firmly positions the diaghragm 16 against the housing
member 14. However, a small amount of fluid remains in the chamber
20 between the corrugations of the diaphragm 16. The plug 88 is
resistance welded into the hole 86 while being submerged in the
expelled perfluorocarbon fluid to prevent the introduction of air
into the chamber 20. The 10 to 20 psig nitrogen gas pressure is
then removed and the pressure chamber subassembly cools to room
temperature thus causing a "mechanical" volume of the chamber 20 to
increase slightly due to the spring back in the diaphragm 16 and
also causing the fluid volume of the perfluorocarbon fluid to
reduce slightly due to the bulk temperature coefficient. The total
of these two volume changes causes a small fluid vapor bubble to be
formed in the chamber 20 that is equal in size to this total volume
change. This vapor bubble acts as a nucleation site to initiate
immediate and proper vaporization of the perfluorocarbon fluid as
medication is removed from the chamber 18 and the diaphragm 16
moves away from the housing member 14.
After the chamber 20 is filled the plug 88 is resistance welded
into the housing member 14 to seal the perfluorocarbon fluid into
the chamber 20. Since this seal cannot be leak tested, a redundant
seal is provided by TIG, laser or electron beam welding a thin
piece of titanium 90 over the plug 88, as shown in FIG. 8, before
the subassembly comprising the housing member 14 and the diaphragm
16 is assembled to the member 12. After the sealing plate 90 has
been welded in place, this subassembly is sealed to the outer edge
portion 92 of the upper housing member 12 by TIG, laser or electron
beam meltdown welding to provide the completed housing 10. However,
before this operation, a leak testable seal is established between
the neck portion 24 and the upper housing member 12. More
particularly, before the members 12, 14 are welded together, the
body stem 36 is first welded to the neck portion 24 as indicated by
the weld 94 (FIG. 7) before the neck portion 24 is brazed or
resistance welded to the member 12. After the body stem 36 has been
welded to the neck portion 24 the neck portion is brazed or
resistance welded to the member 12 and the body stem 36 is also
welded to the member 12 by means of the weld 96. After these
operations have been performed the housing member 14 is then welded
to the outer lip portion 92 of the member 12.
As discussed heretofore, it is also possible to use Freon 11, also
called Freon MF, which is produced by the E. I. DuPont Company and
has a vapor pressure equal to 23 psia at 98.6.degree. F., in place
of the FC-87 or FC-88 perfluorocarbon fluid (vapor pressure of 17.5
psia at 98.6.degree. F.). The same filling procedure described in
detail above for the perfluorocarbon fluid is employed to fill the
pressure stabilizing chamber 20 with Freon 11. When the chamber 20
is filled with Freon 11 the undesired variation of infusion rate
due to altitude and temperature changes is greatly reduced, as
described heretofore.
In order to protect the patient against any possible injury due to
sharp edges of the housing 10, a silicone cover 98 is placed over
the outer edge of the housing 10, the cover 98 extending around the
entire periphery of the housing 10 to a point adjacent the body 22,
as is clearly illustrated in FIG. 1.
Considering now the manner in which medication in the reservoir 18
is forced through the unit 40 and out of the manifold body 22, the
integral filter and capillary unit 40 is provided with the
transverse inlet opening 100 in one corner thereof which is
positioned above a quadrant shaped recess 102 in the bottom wall of
the chamber 34. The unit 40 is also provided with a transverse,
central outlet opening 104 which is positioned above the transverse
end portion 106 of a passageway 108 provided in the body 22. The
O-ring 42 provides a seal between the inlet 100 and the outlet 104
of the unit 40. Alternatively, an additional O-ring concentric with
O-ring 42 can be used to provide a redundant O-ring seal. If
desired, the recess 102 may be in the form of an annular recess in
the bottom wall of the chamber, this annular recess permitting
access to the inlet 100 irrespective of the orientation of the unit
40 within the chamber 34.
The passageway 108 communicates with a side opening recess 110
which is provided in the body 22 and is adapted to receive a
catheter assembly, as shown in FIG. 1. More particularly, this
catheter assembly comprises a main body member 112 which is sealed
within the recess 110 by means of the O-ring 114 and is held in
place by the set screw 116. The body 112 is preferably made of
medical grade silicone elastomer, or other biocompatible material,
and is provided with the central passageway 118 which extends to
the flexible catheter tube 120 the end of which is secured in an
end recess in the body 112 by any suitable means such as by a
silicone adhesive or by a vulcanizing process. A tapered sleeve 122
is provided to prevent excessive bending of the catheter tube 120
when it is placed at the desired infusion site within the body. It
will be noted that during the supply of medication through the unit
40 to the catheter outlet the medication flows in the reverse
direction through the passageway 32 from that of the filling
operation. Preferably, all of the component parts of the
implantable medication infusion device of the present invention,
except for the septum 60, flow restrictor unit 40 and catheter 112,
are made of titanium which is more compatible, both to the
medication and to the body, than a stainless steel or a titanium
alloy.
Considering now the integral filter and capillary unit 40, and
referring to FIGS. 5 and 6 wherein this unit is shown on a greatly
expanded scale, the unit 40 comprises a square silicon substrate
130 approximately 3/8 of an inch on each side and having a
thickness of about 0.010 inches. The substrate 130 is
electrostatically bonded to a glass plate 132 of a size similar to
the substrate 130 and having a thickness of about 0.040 inches. The
plate 132 is provided with the transverse inlet opening 100 and
outlet opening 104 which communicate with different grooved areas
on the substrate 130. More particularly, the inlet opening 100
communicates with a collector channel 134 which is positioned
between two groups of transversely extending, parallel inlet filter
grooves 136 and 138 formed in the surface of the substrate 130.
Medication which is forced through the filter grooves 136, 138 is
collected in the collector channels 140, 142 and 144 formed in the
surface of the substrate 130, which supply filtered medication to
the inlet of a capillary groove 146 which is formed in the surface
of the substrate 130 and extends in a series of reentrant loops to
an outlet portion 148 thereof. The outlet 148 of the capillary
groove 146 communicates with collector channels 150, 152, 154 and
156 also formed in the surface of the substrate 130. The collector
channels 150-156 communicate with four groups of parallel outlet
filter grooves 158, 160, 162 and 164 which are arranged around the
four sides of the rectangular outlet collector area 166 formed in
the surface of the substrate 130 at the center thereof. Medication
which then passes through the outlet filter grooves 158-164 is
collected in the area 166 and supplied through the transverse
outlet 104 in the glass plate 132, and through the channel 108 in
the body 22 to the catheter outlet described heretofore. All of the
above described grooves, channels and collector areas are
preferably formed in the surface of the silicon substrate 130 by a
single operation using semiconductor processing and micromachining
techniques, as described in detail in the aoove identified Barth
application Ser. No. 616,658 and in an article entitled "Silicon
Micromechanical Devices" by James B. Angell, Stephen C. Terry and
Phillip W. Barth which appeared in the April, 1983 issue of
Scientific American, pp. 44-55. The substrate 130 is preferably a
single silicon crystal in which the [100] plane is oriented
parallel to the surface of the substrate 130 in which the grooves
and collector channels are formed. Also, an anisotropic etchant is
preferably employed which etches at different rates in different
directions in the crystal lattice so that sharp edges and corners
are formed during the etching process. Suitable anisotropic
etchants are hot alkaline solutions such as aqueous potassium
hydroxide (KOH), aqueous sodium hydroxide (NaOH) and a mixture of
ethylenediamine, pyrocatechol, and water, known as EDP. As
described in detail in the above identified Angell et al article,
with such ansiotropic etchants flat bottomed grooves can be formed
in a [100] crystal by stopping the etching operation before the
point of intersection of the [111] planes is reached. Accordingly,
by starting with exposed areas of different widths for the inlet
filter grooves 136, 138, the outlet filter grooves 158-164, the
capillary groove 146 and the collector channels, all of the grooves
and collector channels may be formed in a single etching operation.
More particularly, as shown in FIG. 9, as the etching operation
proceeds the sidewalls of the grooves slope inwardly along the
[111] planes of the substrate 130 but the bottom of the groove
remains parallel to the surface of this substrate. Thus,
considering the capillary groove 146, at the start of the etching
operation the bottom of the groove is shown by the dotted line
146a, the final groove being shown in solid lines in this figure as
having the narrower flat bottom portion 146b. With regard to the
inlet filter grooves 136, which are initially much narrower than
the capillary groove area, in the early portion of the etching
process the flat bottom portion 136a is produced, as shown in
dotted lines in FIG. 9. However, before the end of the etching
operation the point of intersection of the [111] planes is reached
to provide a sharp V groove which is shallower than the capillary
groove 146. In a similar manner, the outlet filter grooves 158
which are somewhat wider than the inlet filter grooves 136 have the
initial flat bottom portion 158a at the beginning of the etching
operation. However, by the end of the etching operation the deeper
sharp V groove 158 is formed which is of the same depth as the
capillary groove 146 and is of substantially greater cross
sectional area than the inlet filter grooves 136. The collector
channels 150 are also formed during the same etching operation and
have a much wider flat bottom portion since they are of
substantially greater width than the capillary groove 146.
Preferably, the cross sectional area of the inlet filter grooves
136, 138 is substantially smaller than the cross sectional area of
the outlet filter grooves 158-164. With such an arrangement the
outlet filter grooves 158-164 can trap particles which might plug
the capillary under backflow conditions wnich could occur during
construction and testing of the implantable device of FIG. 1.
However, the outlet filter grooves 158-164 should not clog with
particles which are small enough to pass through the inlet filter
grooves 136, 138 and the capillary groove 146 in the normal flow
direction. Preferably the inlet filter grooves 136, 138 are 28
microns wide, the outlet filter grooves 158-164 are 39 microns
wide, and the capillary groove 146 is 50 microns wide, 20 microns
deep and 6.4 inches long for a nominal (98.6.degree. F., sea level)
infusion rate of 10 microliters per hour of 100 unit insulin. All
of the wall portions of the grooves 136, 138, 158-164 and 146 slope
inwardly and downwardly at an angle of 54.74 degrees relative to
the horizontal, i.e. along the [111] plane of the crystal substrate
130. The number of inlet filter grooves 136, 138 is preferably such
that the total flow area of these grooves is about 120 times the
flow area of the capillary groove 146. The number of outlet grooves
158-164 is such that the total flow area of these grooves is about
200 times the flow area of the capillary groove 146.
The substrate 130 and glass plate 132 are preferably bonded by
providing optically flat surfaces on the opposed surfaces of these
parts. They are then heated to a temperature of about 400.degree.
C. and a potential of about 1200 volts DC is applied across the
assemoled parts 130 and 132 for about 15 minutes to create an
electrostatic bonding force. During this bonding operation the
negative terminal of the 1200 volt D.C. supply is connected to the
glass plate 132. The parts may either be heated first and then the
voltage applied or the voltage may be applied and the parts then
heated. No external pressure is applied in such an electrostatic
bonding operation and very little stress is produced as a result
thereof because both the substrate 130 and the glass plate 132 have
substantially the same temperature coefficient of expansion.
Preferably, the glass plate 132 is a tybe 7740 Pyrex borosilicate
glass manufactured by Corning Glass Works.
Preferably, a large number of the silicon substrates 130 are formed
from a single large silicon wafer so that inlet and outlet filter
grooves and the capillary groove 146 are of highly uniform
dimensions and the substrates 130 formed from the common wafer will
have substantially identical flow rates through the capillary
groove 146 thereof. After this large wafer is completed in
accordance with the processing technique described above, a glass
plate of similar size is electrostatically bonded to the wafer, as
described heretofore, and the resultant multilayer unit is then
diced into squares by a diamond saw to provide the units 40. With
such an arrangement different flow rates may be accurately provided
for a large number of units 40 by simply varying the initial width
of the unmasked area of the substrate surface corresponding to the
capillary groove 146 or by changing the etching time and depth of
the capillary groove. It is thus ppssible to provide implantable
devices having accurately predetermined flow rates by simply
choosing a unit 40 having a desired flow rate of 10 microliters per
hour, 15 microliters per hour, etc. and mounting it in the body 22
in the manner described in detail heretofore.
During the dicing operation tape is placed over the holes 100 and
104 in the glass plate 132 to prevent contamination of the filter
grooves by the duct from the diamond saw. The holes 100 and 104 in
the glass plate 132 may either be made mechanically by an abrasive
vapor blasting technique or they can be laser drilled. In either
case, tne holes 100 and 104 will be tapered inwardly somewhat when
formed using these techniques, as will be readily understood by
those skilled in the art.
If desired, the integral filter and capillary unit 40 may be
mounted in the chamber 34 with the silicon substrate 130 on the
bottom adjacent the passage 106 in the manifold 22. In such case,
openings corresponding to the holes 100 and 104 are provided in the
silicon substrate 130 rather than in the glass plate 132.
In accordance with an alternaive embodiment of the invention, the
capillary groove 146 may be replaced by a multiple orifice
restrictor arrangement, as shown in FIGS. 10, 11 and 12 in order to
reduce the above described variation in infusion rate due to
altitude and temperature changes. Referring to these figures, a
series of miniature orifices are formed in the silicon substrate
170 which is preferably a single silicon crystal in which the [100]
plane is oriented parallel to the surface of the substrate 170.
These miniature orifices are formed in the substrate 170 by first
anisotropically etching the tranverse V shaped channels 172 which
are positioned along the flow path of the multiple orifice
restrictor unit. The channels 172 have sloping side walls 174 and
176 and sloping end walls 178 and 180 all of which extend
downwardly at an angle of 54.74.degree. to the horizontal along the
[111] plane of the crystal 170. The channels 172 preferably have a
transverse length at the surface of the substrate 170 of 90 microns
and a width along the flow path of 69 microns. Each channel 172 is
separated from the next one by 2 microns.
Before the channels 172 are formed in the substrates 170, a series
of staggered orifices are initially formed in the surface of
substrate 170 in the areas separating the transversely extending
channels 172 by anisotropically etching the small longitudinally
extending V-shaped grooves 182. The grooves 182 have a width of 8
microns and are etched to a depth of 5.7 microns (0.00022 inches),
the walls thereof sloping inwardly at an angle of 54.74.degree. to
the horizontal. Preferably, the initial surface areas provided to
form the grooves 182 will have a width of 8 microns and a length
along the flow path of approximately 15 microns, the sloping end
walls of the grooves 182 being etched away when the grooves 172 are
formed, so that the final shape of the grooves 182 is as
illustrated in FIGS. 10, 11 and 12. When the glass plate 184 is
placed on the upper surface of the substrate 170 and bonded
thereto, in the manner described heretofore in connection with the
integral filter and capillary unit 40, a series of microminiature
precision orifices are formed by the V-shaped longitudinally
extending grooves 182 which are of extremely small dimensions and
are much smaller and dimensionally more accurate than would be
possible by conventional metal machining or chemical milling in a
metal such as titanium. As clearly shown in FIG. 10, the grooves
182 are preferably staggered along the length of the walls
separating the channel 172 to provide additional flow
restriction.
In the embodiment of FIGS. 10, 11 and 12 the transverse channels
172 extend along a flow path generally similar to the reentrant
path of tne capillary groove 146 in the substrate 130 of FIGS. 5
and 6. At the right angle turns of the flow path of FIGS. 10, 11
and 12 a square, flat bottomed channel 186 is formed in the
substrate 170 by anisotropic etching at the same time the V-shaped
channels 172 are formed, the channel 186 having the four sloping
wall portions 188, 190, 192 and 194 which extend along the [111]
plane of the crystal at an angle of 54.74 degrees relative to the
horizontal. The small V-shaped orifice grooves 182 are then formed
in the wall portions 188 and 194 of the channel 186 at the same
time the rest of the grooves 182 are formed in the substrate
170.
In the embodiment of FIGS. 10, 11 and 12 the substrate 170 and
glass plate have the same overall dimensions as the unit 40
described in detail heretofore. Also, the inlet filter grooves 136,
138, outlet filter grooves 156-164 and collector channels 134, 140,
142, 144 and 150-156 are all formed in the substrate 170 at the
same time the V-shaped channels 172 are formed therein. However,
both the inlet filter grooves 136, 138 and the outlet filter
grooves 156-164 are considerably narrower in the embodiment of
FIGS. 10, 11 and 12 to provide proper filtering for the orifices
formed by the V-grooves 182. Preferably, the inlet filter grooves
136, 138 have a width of 4 microns and the outlet filter grooves
156-146 have a width of 6 microns in the multiple orifice
embodiment of FIGS. 10, 11 and 12.
As discussed generally heretofore, the flow rate through an
orifice, such as the orifices formed by the V-grooves 182 in the
substrate 170, is proportional to the square root of the pressure
drop across the orifice whereas the flow rate in the capillary
groove 146 of FIGS. 5 and 6 is directly proportional to the
pressure drop thereacross. Accordingly, for a given change in the
pressure drop across the restrictor, due to altitude and
temperature variations, the variation in flow rate of the mutliple
orifice restrictor of FIGS. 10, 11 and 12 will be substantially
less than the capillary groove arrangement of FIGS. 5 and 6. For
example, a change in pressure when traveling from sea level to
10,000 feet altitude may cause the flow rate of the capillary
groove arrangement of FIGS. 5 and 6 to vary by a factor of 2.5
(with an FC-87 pressurant) whereas this change in pressure would
theoretically cause the flow rate of the multiple orifice
arrangement of FIGS. 10, 11 and 12 to vary oy only a factor of 1.6.
This factor is closer to 1.7 in actual practice due to the
imperfect orifice conditions around the grooves 182. Nevertheless,
it will be seen that a substantial reduction in the undesired
variation of flow rate with changes in altitude and temperature is
achieved with the embodiment of FIGS. 10, 11 and 12.
Since the infusion rate of an implantable device is very slow,
there is a very low velocity pressure developed by each of the
orifices in the embodiment of FIGS. 10, 11 and 12 and a large
number of orifices is required to create a sufficient pressure
drop. For example, when the grooves 182 have the dimensions and
spacing described heretofore, approximately 2530 orifices are
required to limit the infusion rate to 10 microliters per hour
using FC-87 or FC-88 perfluorocarbon pressurant at normal body
temperature, i.e. 98.6.degree. F.
While there have been illustrated and described several embodiments
of the present invention, it will be apparent that various changes
and modifications thereof will occur to those skilled in the art.
It is intended in the appended claims to cover all such changes and
modifications as fall within the true spirit and scope of tne
present invention.
* * * * *